The emergence of an outbreak of Monkeypox disease (MPXD) is caused by a contagious zoonotic Monkeypox virus (MPXV) that has spread globally. Yet, there is no study investigating the effect of climatic changes on MPXV transmission. Thus, studies on the changing epidemiology, evolving nature of the virus, and ecological niche are highly paramount. Determination of the role of potential meteorological drivers including temperature, precipitation, relative humidity, dew point, wind speed, and surface pressure is beneficial to understand the MPXD outbreak. This study examines the changes in MPXV cases over time while assessing the meteorological characteristics that could impact these disparities from the onset of the global outbreak. To conduct this data-based research, several well-accepted statistical techniques including Simple Exponential Smoothing (SES), Auto-Regressive Integrated Moving Average (ARIMA), Automatic forecasting time-series model (Prophet), and Autoregressive Integrated Moving Average with Explanatory Variables (ARIMAX) were applied to delineate the correlation of the meteorological factors on global daily Monkeypox cases. Data on MPXV cases including affected countries spanning from 6 May 2022, to 9 November 2022, from global databases and meteorological data were used to evaluate the developed models. According to the ARIMAX model, the results showed that temperature, relative humidity, and surface pressure have a positive impact [(51.56, 95% confidence interval (CI): -274.55 to 377.68), (17.32, 95% CI: -83.71 to 118.35) and (23.42, 95% CI: -9.90 to 56.75), respectively] on MPXV cases. In addition, dew/frost point, precipitation, and wind speed show a significant negative impact on MPXD cases. The Prophet model showed a significant correlation with rising MPXD cases, although the trend predicts peak values while the overall trend increases. This underscores the importance of immediate and appropriate preventive measures (timely preparedness and proactive control strategies) with utmost priority against MPXD including awareness-raising programs, the discovery, and formulation of effective vaccine candidate(s), prophylaxis and therapeutic regimes, and management strategies.